We have recently found increased glucagon secretion but normal insulin release by isolated pancreatic islets obtained from rats fed a high protein, carbohydrate-free (HP) diet. The elevated glucagon secretion cannot be suppressed by high concentrations of glucose in the medium. Since similar alterations of glucagon secretion occur in diabetes mellitus, it is important to understand the mechanisms by which glucagon synthesis and release are controlled. We will study precursor incorporation into glucagon by isolated islets of rats fed different diets. Stimulators and inhibitors of glucagon secretion will be used to determine their influence on alpha cell function. The effects of meal-feeding on hepatic gluconeogenesis and insulin and glucagon secretion will be investigated. Although it has been reported that gluconeogenesis is enhanced by meal-feeding, we intend to reexamine the matter using the isolated, perfused rat liver since responses of this preparation are similar to those which occur in vivo. Hepatic CAMP and amino acid transport are increased by mean feeding, findings which suggest that glucagon production is augmented. Since insulin and glucagon secretion have not been directly measured, we will determine plasma concentrations and islet secretion of these hormones in meal-fed and normally-fed rats.